Azopt combination with timolol is effective at lowering IOP, study finds

IOP reduction was close to 5% when brinzolamide was used adjunctively with timolol. Patients reported less eye discomfort than with dorzolamide.

PRAGUE — Azopt (brinzolamide, Alcon) is as effective as Trusopt (dorzolamide, Merck) in reducing intraocular pressure when used in combination with timolol, according to a recent study.

The glaucoma drug Azopt, a topical carbonic anhydrase inhibitor similar to dorzolamide, produced an average additional intraocular pressure (IOP) reduction of 4.5 mm Hg when used in combination with timolol. Details of the study were presented at the International Glaucoma Symposium here.

The only significant difference between the two drugs was the rate of reported ocular discomfort, which was lower in patients receiving brinzolamide, according to study principal investigator Peter K. Wishart, MB, ChB, of the Royal Liverpool Hospital.

“We conclude that brinzolamide is significantly more comfortable than dorzolamide,” Dr. Wishart said.

Equivalent IOP reduction

“Brinzolamide produces significant IOP changes, almost a 5% reduction from baseline IOP. And this reduction is equivalent to dorzolamide. [Brinzolamide] is safe and well-tolerated,” Dr. Wishart said.

The 3-month study at 32 centers in Europe and Australia evaluated 241 patients with open-angle glaucoma or ocular hypertension. The overall performance of the two compounds, 1% brinzolamide or 2% dorzolamide twice daily used as adjunctive therapy to timolol 0.5%, also twice daily, was compared in the double-masked, parallel, actively controlled study.

“Our study design was rigorous; it began with a 3-week run-in on timolol 0.5%. There were two eligibility visits 1 week apart to determine the baseline IOP and then three follow-up visits at months 1, 2 and 3,” Dr. Wishart said.

Both drugs reduced IOP an average of an additional 4.5 mm Hg as adjunctive therapy. Peak reduction was 4.9 mm Hg to 5.3 mm Hg for Azopt and 4.6 mm Hg to 5.1 mm Hg for dorzolamide. IOP differences at trough were similar.

“They’re both very effective, producing on average 4.5 mm Hg of pressure reduction when added to timolol, and there is a slightly greater effect, which is not significant, with brinzolamide,” he said.

Primary outcome

Mean IOP change from baseline morning IOP readings in patients on timolol was the primary outcome measurement.

For inclusion, IOP readings prior to instillation of the morning dose of timolol had to be between 23 mm Hg and 36 mm Hg and had to fall within that range 2 hours after instillation of timolol.

Patients with more than 5 mm Hg variation between eyes were excluded from the study, as were patients with contraindications to any study drugs, eye surgery within 6 months before the study, trauma or monocular status.

Responder rate

Rates of response to therapy were similar for the two drugs. A responder was defined as any patient who, as a result of the additional medication, demonstrated an IOP reduction to below 21 mm Hg or who demonstrated a reduction of 5 mm Hg or greater.

Response rates were 50% to 89% for patients on brinzolamide and 44% to 85% for patients who received dorzolamide, Dr. Wishart said.

He listed the different percentage rates because trough and peak measurements were recorded for each group at 1 month, 2 months and 3 months.

“The biggest reduction was at right about the 2-month period, where 88% of the brinzolamide patients were controlled,” he said.

Adverse events

Seven adverse events were reported with brinzolamide and 34 adverse events in the dorzolamide group, Dr. Wishart reported.

“The most frequent adverse events with brinzolamide were ocular discomfort, at a rate of 1.7%. With dorzolamide, however, burning and stinging were present in 13.1% of patients, including hyperemia present in 3.3%, tearing in 2.5%, ocular pruritis and itching in 1.6%,” he said.

In the brinzolamide group, 2.7% of patients had other ocular adverse events such as eye pain, corneal erosion and keratopathy. Blepharitis, lid spasms, ocular fatigue, keratoconjunctivitis and decreased visual acuity were recorded in 4.8% of the dorzolamide group.

As for systemic side effects, both drugs were about equal, with five patients requiring discontinuance in the brinzolamide group and seven in the dorzolamide group.

Visual acuity, visual fields, optic nerve features and systolic blood pressure measurements were not different in either treatment group, he added.

By measurement of adverse events, however, Dr. Wishart characterized the brinzolamide group as significantly more comfortable.

For Your Information:

Peter K. Wishart, MB, ChB, can be reached at Royal Liverpool Hospital, Prescot St., Liverpool, L7 8XP, England; +(44) 151-706-3698; fax: +(44) 151-706-5861; e-mail: Tejpal@binternet.com.

Alcon Pharmaceuticals, makers of Azopt, can be reached at 6201 South Freeway, Fort Worth, TX 76134 U.S.A.; fax: +(1) 817-241-0677.

Merck & Co., makers of Trusopt, can be reached at 351 North Sumneytown Pike, North Wales, PA 19454 U.S.A.; +(1) 267-305-7896; fax: +(1) 267-305-4283.